ES2966825T3 - Activadores de piruvato quinasa para su uso en el tratamiento de trastornos sanguíneos - Google Patents
Activadores de piruvato quinasa para su uso en el tratamiento de trastornos sanguíneos Download PDFInfo
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- ES2966825T3 ES2966825T3 ES18766063T ES18766063T ES2966825T3 ES 2966825 T3 ES2966825 T3 ES 2966825T3 ES 18766063 T ES18766063 T ES 18766063T ES 18766063 T ES18766063 T ES 18766063T ES 2966825 T3 ES2966825 T3 ES 2966825T3
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2017097496 | 2017-08-15 | ||
| US201862673533P | 2018-05-18 | 2018-05-18 | |
| US201862673526P | 2018-05-18 | 2018-05-18 | |
| PCT/US2018/000127 WO2019035863A1 (en) | 2017-08-15 | 2018-08-15 | PYRUVATE KINASE ACTIVATORS FOR USE IN THE TREATMENT OF HEMATOLOGICAL DISORDERS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2966825T3 true ES2966825T3 (es) | 2024-04-24 |
Family
ID=63524352
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18766400T Active ES2944545T3 (es) | 2017-08-15 | 2018-08-15 | Moduladores de piruvato quinasa y uso de los mismos |
| ES18779068T Active ES2905100T3 (es) | 2017-08-15 | 2018-08-15 | Activadores de piruvato quinasa para su uso en el tratamiento de trastornos sanguíneos |
| ES18766063T Active ES2966825T3 (es) | 2017-08-15 | 2018-08-15 | Activadores de piruvato quinasa para su uso en el tratamiento de trastornos sanguíneos |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18766400T Active ES2944545T3 (es) | 2017-08-15 | 2018-08-15 | Moduladores de piruvato quinasa y uso de los mismos |
| ES18779068T Active ES2905100T3 (es) | 2017-08-15 | 2018-08-15 | Activadores de piruvato quinasa para su uso en el tratamiento de trastornos sanguíneos |
Country Status (32)
| Country | Link |
|---|---|
| US (7) | US11464775B2 (pl) |
| EP (4) | EP3668512B1 (pl) |
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Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE049979T2 (hu) | 2017-03-20 | 2020-11-30 | Forma Therapeutics Inc | Pirrolopirrol készítmények piruvát-kináz (PKR) aktivátorokként |
| ES2944545T3 (es) | 2017-08-15 | 2023-06-22 | Agios Pharmaceuticals Inc | Moduladores de piruvato quinasa y uso de los mismos |
| CN113226356A (zh) | 2018-09-19 | 2021-08-06 | 福马治疗股份有限公司 | 活化丙酮酸激酶r |
| BR112021005188A2 (pt) | 2018-09-19 | 2021-06-08 | Forma Therapeutics, Inc. | tratamento de anemia falciforme com um composto de ativação de piruvato cinase r |
| MA54948A (fr) * | 2019-02-13 | 2021-12-22 | Agios Pharmaceuticals Inc | Dérivés thiéno[3,2-b]-pyrrole[3,2-d]pyridazinones et leur utilisation comme dérivés de pkm2 pour le traitement de troubles associés au cancer, à l'obésité et au diabète |
| WO2020262419A1 (ja) * | 2019-06-26 | 2020-12-30 | 日産化学株式会社 | 電荷輸送性ワニス |
| WO2022020424A1 (en) * | 2020-07-21 | 2022-01-27 | The Regents Of The University Of Michigan | Compositions and methods for activating pyruvate kinase |
| CN112490502B (zh) * | 2020-12-04 | 2022-01-21 | 广州天赐高新材料股份有限公司 | 一种电解液及锂二次电池 |
| WO2022170200A1 (en) | 2021-02-08 | 2022-08-11 | Global Blood Therapeutics, Inc. | 1-(2-sulfonyl-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4h)-yl]-ethanone derivatives as pyruvate kinase (pkr) and pkm2 activators for the treatment of sickle cell disease |
| CN118139864A (zh) * | 2021-09-30 | 2024-06-04 | 西特瑞治疗有限公司 | 新化合物 |
| IL312679A (en) * | 2021-11-16 | 2024-07-01 | Agios Pharmaceuticals Inc | Compounds for the treatment of anemia associated with MDS and other conditions |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4405635A (en) | 1979-06-18 | 1983-09-20 | Merrell Dow Pharmaceuticals Inc. | 4-Aroylimidazol-2-ones and their use as pharmaceuticals |
| US4883914A (en) | 1987-08-17 | 1989-11-28 | American Cyanamid Company | Benzenesulfonyl carboxamide compounds useful as herbicidal agents |
| EP1218373A2 (en) | 1999-07-30 | 2002-07-03 | Basf Aktiengesellschaft | 2-pyrazolin-5-ones as tyrosine kinase inhibitors |
| TR200200550T2 (tr) | 1999-09-04 | 2002-06-21 | Astrazeneca Ab | Piruvat dehidrojenaz aktivitesini yükselten ikameli n-fenil 2-hidroksi -2- metil -3,3,3- triflüoropropanamid türevleri. |
| EP1972629A1 (en) * | 2007-03-23 | 2008-09-24 | Mutabilis SA | New imidazolo-heteroaryl derivatives with antibacterial properties |
| FR2933983B1 (fr) * | 2008-07-15 | 2010-08-27 | Servier Lab | Nouveaux derives tricycliques,leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| EP2318408B1 (en) * | 2008-07-23 | 2016-02-17 | Vertex Pharmaceuticals Incorporated | Tri-cyclic pyrazolopyridine kinase inhibitors |
| US8420649B2 (en) * | 2008-08-29 | 2013-04-16 | Amgen Inc. | Pyrido[3,2-d]pyridazine-2(1H)-one compounds as p38 modulators and methods of use thereof |
| AU2009303335B2 (en) | 2008-10-09 | 2016-05-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Activators of human pyruvate kinase |
| EP2417123A2 (en) * | 2009-04-06 | 2012-02-15 | Agios Pharmaceuticals, Inc. | Therapeutic compositions and related methods of use |
| CN102481300B (zh) | 2009-06-29 | 2015-04-15 | 安吉奥斯医药品有限公司 | 治疗性化合物和组合物 |
| WO2011137089A1 (en) | 2010-04-29 | 2011-11-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Activators of human pyruvate kinase |
| US20130252963A1 (en) | 2010-12-06 | 2013-09-26 | Yun Jin | Pyrimidinone compounds for use in the treatment of disease or conditions mediated by lp-pla2 |
| TWI549947B (zh) | 2010-12-29 | 2016-09-21 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
| CA2834692A1 (en) * | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc. | Pyruvate kinase activators for use in therapy |
| WO2012151448A1 (en) * | 2011-05-03 | 2012-11-08 | Agios Pharmaceuticals, Inc. | Pyruvate kinase activators for use in therapy |
| PL3406251T3 (pl) * | 2011-05-03 | 2024-04-29 | Agios Pharmaceuticals, Inc. | Aktywatory kinazy pirogronianowej do stosowania w terapii |
| ES2829374T3 (es) | 2011-05-03 | 2021-05-31 | Agios Pharmaceuticals Inc | Uso de activadores de piruvato quinasa para aumentar la vida útil de los glóbulos rojos de la sangre y tratar la anemia |
| CN103930422A (zh) * | 2011-07-19 | 2014-07-16 | 无限药品股份有限公司 | 杂环化合物及其用途 |
| WO2013056153A1 (en) * | 2011-10-13 | 2013-04-18 | Kung Charles | Activators of pyruvate kinase m2 and methods of treating disease |
| WO2014018851A1 (en) | 2012-07-26 | 2014-01-30 | Joslin Diabetes Center, Inc. | Predicting and treating diabetic complications |
| AU2013342203B2 (en) | 2012-11-08 | 2017-11-23 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions and their use as PKM2 modulators |
| JP2016506943A (ja) * | 2013-01-30 | 2016-03-07 | バイエル・ファルマ・アクティエンゲゼルシャフト | Ｍｋｎｋ−１キナーゼ阻害剤としてのアミドイミダゾピリダジン類 |
| MX365950B (es) | 2013-03-13 | 2019-06-19 | Flatley Discovery Lab Llc | Compuestos de piridazinona y metodos para el tratamiento de la fibrosis quistica. |
| WO2014139144A1 (en) | 2013-03-15 | 2014-09-18 | Agios Pharmaceuticals, Inc. | Therapeutic compounds and compositions |
| AR097543A1 (es) * | 2013-09-06 | 2016-03-23 | Lexicon Pharmaceuticals Inc | COMPUESTOS BASADOS EN IMIDAZO[1,2-b]PIRIDAZINA, COMPOSICIONES QUE LOS COMPRENDEN Y SUS MÉTODOS DE USO |
| JP7235742B2 (ja) | 2017-07-07 | 2023-03-08 | インフレイゾーム リミテッド | 新規なスルホンアミドカルボキサミド化合物 |
| CA3071150A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as nlrp3 inhibitors |
| ES2944545T3 (es) * | 2017-08-15 | 2023-06-22 | Agios Pharmaceuticals Inc | Moduladores de piruvato quinasa y uso de los mismos |
| AR112475A1 (es) | 2017-08-15 | 2019-10-30 | Agios Pharmaceuticals Inc | Moduladores de piruvato quinasas y uso de los mismos |
| CA3073112A1 (en) | 2017-08-15 | 2019-02-21 | Abbvie Inc. | Macrocyclic mcl-1 inhibitors and methods of use |
| MA54948A (fr) * | 2019-02-13 | 2021-12-22 | Agios Pharmaceuticals Inc | Dérivés thiéno[3,2-b]-pyrrole[3,2-d]pyridazinones et leur utilisation comme dérivés de pkm2 pour le traitement de troubles associés au cancer, à l'obésité et au diabète |
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